We are investigating the renal sympathetic and renin-angiotensin systems by combining ultrastructural, histochemical, and biochemical methods. We have used this approach to study the two-kidney Goldblatt hypertension model in which rats were made hypertensive by producing unilateral renal artery stenosis. Our results indicated that there was a marked reduction of monoaminergic nerve fluorescence and catecholamine tissue content in the ischemic kidney and a normal amount of fluorescence and catecholamine content in the nonischemic kidney. Electron microscopy showed marked reduction in the number of anatomically recongnizable nerves in the ischemic kidney and a normal innervation in the nonischemic kidney. As was expected, increase in renin content and J.G. granularity of the ischemic kidney was accompanied by a marked reduction in renin content and granularity on the nonischemic side. Juxtaglomerular cells were seen in the glomerular mesangium. We are continuing in the investigation of the response of the renal sympathetic system and juxtaglomerular cells to various pharmacological agents by using the same approach. In other studies we have localized ultrastructurally acetylcholinesterase in the rat renal nerves. In this species the renal nerves are known to have the characteristics of adrenergic nerves by fluorescent histochemistry and ultrastructurally. The demonstration of acetylcholinesterase activity in the renal nerves, therefore, supports the view that this enzyme is present in adrenergic nerves.